Seasonal Allergic Rhinitis (SAR)
Conditions
Keywords
GSP 301 nasal spray for the treatment of Seasonal Allergic Rhinitis
Brief summary
Study to evaluate the efficacy, safety and tolerability of GSP 301 nasal spray (NS) compared with placebo NS in pediatric subjects (aged 6 to under 12 years) with Seasonal Allergic Rhinitis (SAR).
Interventions
DRUGGSP 301 NS
1 spray in each nostril twice daily for 14 days
1 spray in each nostril twice daily for 14 days
Sponsors
Glenmark Specialty S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects aged ≥6 to \<12 years 2. Clinical history of SAR (at least 2 years) with exacerbations during the study season for the relevant seasonal allergen (e.g., tree/grass pollen) 3. Demonstrated sensitivity to at least 1 seasonal allergen through positive skin prick test within 12 months prior to screening 4. A 12-hour rTNSS value ≥6 out of a possible 12 for the morning assessment at screening 5. Signed informed consent/assent form (subject and parent/caregiver/legal guardian)
Exclusion criteria
1. Females of childbearing potential or pregnant 2. Plans to travel outside the known pollen area for the investigational site for 24 hours or longer during the last 7 days of the run-in period. 3. History of anaphylaxis and/or other severe local reaction(s) to skin testing 4. History and evidence of acute or significant chronic sinusitis or chronic purulent post nasal drip 5. Subjects with an active pulmonary disorder or infection. 6. Subjects with posterior subcapsular cataracts or glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period | Baseline and day 14 | The Reflective Total Nasal Symptom Score (rTNSS) was assessed by 12-hour reflective scoring of the severity of four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching). Scores ranged from 0 (no signs/symptoms evident) to 3 (severe signs/symptoms that is hard to tolerate, causes interference with activities of daily living and/or sleeping). Each of these four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching) of the rTNSS is rated on a scale from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). The four nasal symptoms of the rTNSS is summed. The total score of the rTNSS ranged from 0 to 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period. | Baseline and day 14 | The instantaneous Total Nasal Symptom Score (iTNSS) was assessed by instantaneous (ie, an evaluation of the symptom severity just before taking study medication \[within 10 minutes\]) of four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching). Scores ranged from 0 (no signs/symptoms evident) to 3 (severe signs/symptoms that is hard to tolerate, causes interference with activities of daily living and/or sleeping). Each of these four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching) of the iTNSS is rated on a scale from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). The four nasal symptoms of the iTNSS is summed. The total score of the iTNSS ranged from 0 to 12. |
| Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4) | Baseline and day 15 | The PRQLQ is a validated, disease-specific, quality-of-life (QOL) questionnaire developed to measure the physical, emotional, and social impairments that are experienced by children (aged ≥6 to \<12 years) with rhinoconjunctivitis. The PRQLQ has 23 questions in 5 domains (nose symptoms, eye symptoms, practical problems, activity limitation and other symptoms). Subjects recall how they have been during the previous week and respond to each question on a 7-point scale with scores ranging from 6 (extremely bothered), 5 (very bothered), 4 (quite bothered), 3 (somewhat bothered), 2 (bothered a bit), 1 (hardly bothered at all), 0 (not bothered). The Overall PRQLQ score is the mean of all 23 subject-reported responses. The Overall PRQLQ score range from 0 to 6 where 0 represents no impairment and 6 represents maximum impairment. |
| Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period. | Baseline and day 14 | The Total Ocular Symptom Score (TOSS) will be calculated using the 3 eye-related non-nasal symptoms: itching/burning eyes, tearing/watering eyes, and redness of eyes. The subject will assess and report his/her non-nasal symptoms twice (AM and PM assessments). Scores ranged from 0 (No sign/symptom evident), 1 (Sign/symptom clearly present but minimal awareness; easily tolerated), 2 (Definite awareness of sign/symptom that is bothersome but tolerable) and 3 (Sign/symptom is hard to tolerate; causes interference with activities of daily living and/or sleeping). The Total Ocular Symptom Score (TOSS) ranged from 0 to 9. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GSP 301 NS Intranasal administration, 1 spray in each nostril BID (AM and PM, approximately 12 hours apart) for 14 days | 225 |
| Placebo NS Intranasal administration, 1 spray in each nostril BID (AM and PM, approximately 12 hours apart) for 14 days | 221 |
| Total | 446 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Investigator/Sponsor Decision | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Use of prohibited medication by subject | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | GSP 301 NS | Placebo NS | Total |
|---|---|---|---|
| Age, Continuous | 8.7 years STANDARD_DEVIATION 1.6 | 8.6 years STANDARD_DEVIATION 1.7 | 8.7 years STANDARD_DEVIATION 1.7 |
| Age, Customized 6 - < 9 | 100 Participants | 99 Participants | 199 Participants |
| Age, Customized 9 - < 12 | 125 Participants | 122 Participants | 247 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 67 Participants | 85 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 135 Participants | 293 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants | 44 Participants | 90 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 168 Participants | 169 Participants | 337 Participants |
| Sex: Female, Male Female | 99 Participants | 109 Participants | 208 Participants |
| Sex: Female, Male Male | 126 Participants | 112 Participants | 238 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 225 | 0 / 221 |
| other Total, other adverse events | 0 / 225 | 0 / 221 |
| serious Total, serious adverse events | 0 / 225 | 1 / 221 |
Outcome results
Primary
Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period
The Reflective Total Nasal Symptom Score (rTNSS) was assessed by 12-hour reflective scoring of the severity of four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching). Scores ranged from 0 (no signs/symptoms evident) to 3 (severe signs/symptoms that is hard to tolerate, causes interference with activities of daily living and/or sleeping). Each of these four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching) of the rTNSS is rated on a scale from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). The four nasal symptoms of the rTNSS is summed. The total score of the rTNSS ranged from 0 to 12.
Time frame: Baseline and day 14
Population: The Full Analysis Set (FAS) consisted of all subjects who are randomized and received at least 1 dose of IP and had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period | Baseline | 8.83 units on a scale | Standard Deviation 1.41 |
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period | Mean Change from baseline to end of treatment | -2.2 units on a scale | Standard Deviation 0.17 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period | Baseline | 8.84 units on a scale | Standard Deviation 1.66 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Nasal Symptom Score ( rTNSS) Over the 14-day Treatment Period | Mean Change from baseline to end of treatment | -1.6 units on a scale | Standard Deviation 0.18 |
p-value: 0.00195% CI: [-0.9, -0.2]Mixed Models Analysis
Secondary
Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period.
The instantaneous Total Nasal Symptom Score (iTNSS) was assessed by instantaneous (ie, an evaluation of the symptom severity just before taking study medication \[within 10 minutes\]) of four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching). Scores ranged from 0 (no signs/symptoms evident) to 3 (severe signs/symptoms that is hard to tolerate, causes interference with activities of daily living and/or sleeping). Each of these four nasal symptoms (rhinorrhea, sneezing, nasal congestion, nasal itching) of the iTNSS is rated on a scale from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe). The four nasal symptoms of the iTNSS is summed. The total score of the iTNSS ranged from 0 to 12.
Time frame: Baseline and day 14
Population: The Full Analysis Set (FAS) consisted of all subjects who are randomized and received at least 1 dose of IP and had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period. | Baseline | 7.89 units on a scale | Standard Deviation 1.93 |
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period. | Mean Change from baseline to end of treatment | -1.8 units on a scale | Standard Deviation 0.17 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period. | Baseline | 7.82 units on a scale | Standard Deviation 2.04 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Instantaneous Total Nasal Symptom Score (iTNSS) Over the 14-day Treatment Period. | Mean Change from baseline to end of treatment | -1.1 units on a scale | Standard Deviation 0.17 |
p-value: <0.00195% CI: [-1, -0.3]Mixed Models Analysis
Secondary
Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period.
The Total Ocular Symptom Score (TOSS) will be calculated using the 3 eye-related non-nasal symptoms: itching/burning eyes, tearing/watering eyes, and redness of eyes. The subject will assess and report his/her non-nasal symptoms twice (AM and PM assessments). Scores ranged from 0 (No sign/symptom evident), 1 (Sign/symptom clearly present but minimal awareness; easily tolerated), 2 (Definite awareness of sign/symptom that is bothersome but tolerable) and 3 (Sign/symptom is hard to tolerate; causes interference with activities of daily living and/or sleeping). The Total Ocular Symptom Score (TOSS) ranged from 0 to 9.
Time frame: Baseline and day 14
Population: The Full Analysis Set (FAS) consisted of all subjects who are randomized and received at least 1 dose of IP and had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period. | Baseline | 3.84 units on a scale | Standard Deviation 2.45 |
| GSP 301 NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period. | Mean Change from baseline to end of treatment | -0.8 units on a scale | Standard Deviation 0.14 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period. | Baseline | 3.59 units on a scale | Standard Deviation 2.52 |
| Placebo NS | Change From Baseline in Average AM and PM Subject-reported 12-hour Reflective Total Ocular Symptom Score (rTOSS) Over the 14-day Treatment Period. | Mean Change from baseline to end of treatment | -0.6 units on a scale | Standard Deviation 0.13 |
p-value: 0.23395% CI: [-0.6, 0.1]Mixed Models Analysis
Secondary
Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4)
The PRQLQ is a validated, disease-specific, quality-of-life (QOL) questionnaire developed to measure the physical, emotional, and social impairments that are experienced by children (aged ≥6 to \<12 years) with rhinoconjunctivitis. The PRQLQ has 23 questions in 5 domains (nose symptoms, eye symptoms, practical problems, activity limitation and other symptoms). Subjects recall how they have been during the previous week and respond to each question on a 7-point scale with scores ranging from 6 (extremely bothered), 5 (very bothered), 4 (quite bothered), 3 (somewhat bothered), 2 (bothered a bit), 1 (hardly bothered at all), 0 (not bothered). The Overall PRQLQ score is the mean of all 23 subject-reported responses. The Overall PRQLQ score range from 0 to 6 where 0 represents no impairment and 6 represents maximum impairment.
Time frame: Baseline and day 15
Population: The Full Analysis Set (FAS) consisted of all subjects who are randomized and received at least 1 dose of IP and had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSP 301 NS | Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4) | Baseline | 2.51 units on a scale | Standard Deviation 1.078 |
| GSP 301 NS | Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4) | Mean Change from baseline to end of treatment | -0.8 units on a scale | Standard Deviation 0.08 |
| Placebo NS | Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4) | Baseline | 2.42 units on a scale | Standard Deviation 1.001 |
| Placebo NS | Change From Baseline in the Overall Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) Score on Day 15 (Visit 4) | Mean Change from baseline to end of treatment | -0.5 units on a scale | Standard Deviation 0.08 |
p-value: <0.00195% CI: [-0.5, -0.1]ANCOVA